Organs Made Transparent with New Imaging Technique

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For the first time, scientists have developed a way to make
organs transparent to light while keeping them intact, providing
a detailed glimpse of their inner structure.

Using the new technique, scientists imaged the
neurological wiring in a mouse's brain. The method, known as
CLARITY (Clear Lipid-exchanged Acrylamide-hybridized Rigid
Imaging/Immunostaining/In situ hybridization-compatible
Tissue-hYdrogel), was described online today (April 10) in the
journal Nature.

"Studying intact systems with this sort of molecular resolution
and global scope — to be able to see the fine detail and the big
picture at the same time — has been a major unmet goal in
biology, and a goal that CLARITY begins to address," study leader
Karl Deisseroth, a bioengineer and psychiatrist at Stanford
University, said in a statement. [ Video
- See Transparent Mouse Brain ]

Traditionally, imaging organs like the brain has involved
slicing them into thin sections, which destroys long-distance
connections between cells. Methods for imaging whole, intact
organs exist, but are generally not compatible with methods for
studying genes and other things at the molecular level. The new
technique lets scientists study intact organs at different
scales, from the broad to the very detailed.

Seeing clearly

The method works by removing the fatty tissue that surrounds
cells and makes them opaque, while preserving the tissue's
structure. First, the tissue is soaked in a mixture of chemicals
and heated slightly to form a mesh that holds everything in place
except the fatty parts. The fatty parts are removed from the
tissue by applying an electrical voltage that pulls them out.

This leaves the tissue intact and virtually transparent — clear
enough to read text through. Molecular markers can then be added
to color specific parts of the see-through organ.

Deisseroth and his team used the CLARITY technique to image the
brain of an adult mouse. The technique allowed them to view
far-reaching neuronal connections and local circuitry, as well as
details on the cellular and molecular level.

The scientists then labeled the tissue with molecular markers to
show how well underlying structures were preserved. What's more,
the tissue could be washed and relabeled multiple times. While
most of the work was done in a mouse, scientists also used the
technique to image zebrafish
brains and
postmortem human brains.

Physicist Winfried Denk of the Max-Planck Institute for Medical
Research, in Germany, called the new technique "a big step
forward in the light microscopy of the whole brain," adding that
"it appears to resolve many of the issues that plagued the other
methods used for this purpose."

The researchers say the imaging technique will enable a deeper
understanding of the brain's function in health and disease. The
technique's main limitations are in the microscope optics, not
the transparent tissue itself, they say.

Deisseroth is one of 15 experts in the team that is mapping out
goals for the $100 million project to
map activity in the human brain announced April 2 by
President Barack Obama.